BLOCK 3: IMM: (3.7) B-CELL ACTIVATION

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Questions and Answers

What type of antigens lead to T-cell independent activation of B-cells?

Polysaccharide antigens

Thymus-independent antigens (correct)

Thymus-dependent antigens

Protein antigens

What characteristic do the epitopes of T-cell independent antigens typically have?

They are irregularly spaced on pathogen surfaces.

They are exclusively found in soluble forms.

They are complex and highly variable.

They occur in dense and regular arrays. (correct)

What role do follicular dendritic cells play in the B-cell area?

They store intact antigens and display them to B-cells. (correct)

They produce antibodies for B-cells.

They inhibit B-cell activation.

They activate T-cells directly.

What mechanism allows for the stimulation of B-cell proliferation and differentiation without T cells?

Clustering of BCRs and co-receptors at the B-cell surface Signup and view all the answers

In which B-cell population is T-cell independent activation predominantly seen?

B-1 cells Signup and view all the answers

What is a requirement for B cell activation?

Cross-linking of B-cell receptors Signup and view all the answers

Which component is part of the B-cell receptor complex?

Monomeric IgM Signup and view all the answers

What initiates a cascade of intracellular signals in B cells?

Cross-linking of B-cell receptors Signup and view all the answers

How does naïve B cell activation occur through a TFH?

Through cytokine release and BCR engagement with antigen Signup and view all the answers

What is the consequence of being unable to form germinal centers?

Reduced B cell differentiation Signup and view all the answers

What is the primary function of the B cell co-receptor?

To enhance the signaling of BCR upon antigen binding Signup and view all the answers

Where does somatic hypermutation and affinity maturation occur after B cell activation?

In germinal centers of lymph nodes Signup and view all the answers

What drives B cell activation, differentiation, and isotype switching?

The presence of specific cytokines Signup and view all the answers

What role does CR2 play in the B cell activation process?

It helps cross-link BCR and co-receptor for improved signaling. Signup and view all the answers

Which statement accurately describes the interaction between BCR and soluble antigens?

C3d tagging on soluble antigens enhances BCR cross-linking. Signup and view all the answers

What initiates the phosphorylation of the cytoplasmic tail of CD19?

Tyrosine kinases associated with BCR activation. Signup and view all the answers

Why do naive B cells require help from CD4 TFH cells?

To recognize pathogen-derived peptides through MHC class II. Signup and view all the answers

What is one consequence of BCR binding to antigen?

Internalization of the antigen through endocytosis. Signup and view all the answers

How does the structure of CR2 facilitate its function?

Its elongated and flexible structure allows cross-linking with diverse antigens. Signup and view all the answers

In what form does a naive B cell recognize an antigen?

By binding with its BCR. Signup and view all the answers

What is a key factor for B cell-mediated immunity during primary immune responses?

Conjugation with CD4 TFH cells. Signup and view all the answers

What role do follicular dendritic cells (FDCs) play in the recognition of antigens by naive B cells?

They capture antigens and present them to B cells. Signup and view all the answers

How are antigens with C3d brought to lymph nodes for B cell recognition?

By binding to CR2 on macrophages and FDCs. Signup and view all the answers

What process occurs after antigen activation of B cells in the lymph node?

B cells move towards the T-cell area. Signup and view all the answers

What is the specific interaction that stabilizes the synapse between TFH cells and B cells?

LFA-1 interactions with ICAM-1. Signup and view all the answers

What type of immunoglobulin do plasma cells primarily secrete upon activation?

IgM Signup and view all the answers

What role does CD40L play in the interaction between TFH cells and B cells?

It facilitates B cell survival signals. Signup and view all the answers

Which cellular structure is involved in the reorientation of the cytoskeleton during B-cell activation?

Microtubule-organizing center (MTOC) Signup and view all the answers

What is the primary location of clonal expansion for B cells in the lymph nodes?

Medullary cords Signup and view all the answers

What is the function of the cytoskeleton during the interaction between B cells and TFH cells?

It enables the formation of a stable synapse. Signup and view all the answers

What are the key molecules that are involved in the delivery of cytokines from TFH cells to B cells?

CD40L and soluble cytokines Signup and view all the answers

What is the primary location where B cells undergo affinity maturation and isotype switching?

Germinal center Signup and view all the answers

Which type of cell drives somatic hypermutation in centroblasts within the germinal center?

T follicular helper (TFH) cells Signup and view all the answers

What happens to centrocytes whose B cell receptors (BCRs) peak in affinity for antigen?

They express Bcl-xL and survive Signup and view all the answers

What is a major role of cytokines produced by TFH cells in the immune response?

To guide B cell switching of immunoglobulin isotypes Signup and view all the answers

Which of the following cells represent mature non-dividing B cells in the germinal center?

Centrocytes Signup and view all the answers

What is the consequence for centrocytes that experience mutations reducing their affinity for antigen?

They undergo apoptosis Signup and view all the answers

Which cytokine is recognized as the most potent inducer of terminal B-cell differentiation in humans?

IL-21 Signup and view all the answers

In the germinal center, what are centroblasts primarily responsible for?

Rapidly dividing Signup and view all the answers

What role do follicular dendritic cells (FDCs) play in the germinal center?

They present antigens to centrocytes Signup and view all the answers

Which of the following is NOT a consequence of the interaction between centrocytes and TFH cells?

Inhibition of memory B cell formation Signup and view all the answers

Which part of the germinal center do centrocytes primarily occupy?

Light zone Signup and view all the answers

What is the fate of centrocytes that undergo successful affinity maturation?

They produce high-affinity antibodies Signup and view all the answers

Which process occurs within the germinal center as B cells undergo selection?

Affinity maturation Signup and view all the answers

What allows for the generation of diverse antibodies in B cells?

Somatic hypermutation Signup and view all the answers

The return of cognate pairs to the primary follicle primarily leads to the formation of what structure?

Germinal centers Signup and view all the answers

What is a key characteristic of self-reactive B cell receptors?

They lead to autoimmune conditions if not eliminated. Signup and view all the answers

At what stage do B cells exhibit increased specificity and affinity for antigens?

Upon repeated antigen exposure Signup and view all the answers

Which statement accurately describes the role of T cells in B cell activation?

T cells provide necessary signals for optimal B cell activation and proliferation. Signup and view all the answers

What occurs after the negative selection phase for B cells?

B cells enter positive selection. Signup and view all the answers

Why is affinity maturation important in B cell responses?

It ensures that B cells respond with higher affinity antibodies upon re-exposure to the same antigen. Signup and view all the answers

What happens to immature B cells that do not react to self antigens?

They continue in the developmental pathway and migrate to the bloodstream. Signup and view all the answers

What is the primary difference in negative selection between B cells and T cells?

B cells can undergo receptor editing if they react to self antigens. Signup and view all the answers

What is the result of positive selection for B cells during their development?

B cells that can bind directly to antigens are positively selected. Signup and view all the answers

Which of the following mechanisms allows B cells to modify their B cell receptors if they react to self antigens?

Receptor editing Signup and view all the answers

How do B cells that respond to self antigens compare to T cells in terms of selection?

B cells may undergo editing while T cells are only eliminated. Signup and view all the answers

In terms of B cell development, what characterizes immature B cells?

They can either develop further or be retained based on their interaction with self antigens. Signup and view all the answers

What is the fate of B cells that strongly react with self antigens during development?

They are retained in the bone marrow and may undergo receptor editing. Signup and view all the answers

What happens to B cells that bind to monovalent self-antigens during the selection process?

They become energetic and cannot respond to that antigen. Signup and view all the answers

Which statement best describes receptor editing in B cells?

Receptor editing allows B cells to modify their receptors to reduce self-reactivity. Signup and view all the answers

How does the process of T cell selection differ from B cell selection?

T cell selection focuses on affinity for peptide-major histocompatibility complexes, while B cell selection assesses direct antigen binding. Signup and view all the answers

What role does the lymphoid tissue play in the life cycle of mature B cells?

It facilitates the recirculation of mature B cells for antigen exploration. Signup and view all the answers

What is a characteristic feature of B cells before they leave the bone marrow?

They express only IgM and are negative for IgD. Signup and view all the answers

Study Notes

B-cell Activation

B-cell activation requires cross-linking of the B-cell receptor (BCR).
The BCR complex consists of monomeric IgM bound to antigen, along with Igα and Igβ chains for intracellular signaling.
Multivalent antigens with regularly arrayed epitopes on pathogen surfaces can bind to IgM and cluster BCRs.
B-cell co-receptors, like CD19, synergize with BCR signaling.
Cross-linking of BCR and co-receptor increases the strength and efficiency of intracellular signaling.
Soluble antigens tagged with C3d can also activate B cells by cross-linking BCR and co-receptor.

B-cell Activation with T-cell Help

Effective B-cell mediated immunity often requires help from CD4+ T follicular helper (TFH) cells.
Naive B cells internalize antigen, process it, and present it to T cells via MHC class II.
TFH cells recognize pathogen-derived peptides presented by MHC class II on B cells, leading to B cell activation.
TFH cells synthesize CD40 ligand (CD40L) which interacts with B-cell CD40 receptors.
TFH cells secrete cytokines like IL-21, which further contributes to B-cell activation.

B-cell Independent Activation

T-cell independent activation of B cells (TI) occurs primarily in B-1 cells.
TI antigens typically have dense and regular arrays of epitopes on pathogen surfaces, leading to strong BCR clustering and activation.
TI activation does not require T-cell help, as the dense clustering of BCRs provides sufficient signaling.

Follicular Dendritic Cells (FDCs)

FDCs in the B-cell area store intact antigens and display them to B cells.
FDCs act as antigen-presenting cells for B-cell activation.
FDCs express complement receptors (CR2) that bind antigens tagged with C3d.
This tethering of antigens to FDCs facilitates their presentation to naive B cells.

B-cell Migration and Primary Focus

Antigen-activated B cells move to the T-cell area to find a TFH cell.
Activated B and TFH cells, forming a cognate pair, move to the medullary cords.
This area is known as the primary focus of B-cell expansion.
During this primary focus, B cells undergo clonal expansion and differentiation into IgM-secreting plasma cells.

Germinal Centers and Secondary Focus

Some B cells from the primary focus return to the follicle, forming a germinal center.
The germinal center represents the secondary focus of B-cell expansion.
Germinal centers are sites where B cells undergo affinity maturation and isotype switching.

Germinal Center Anatomy

Germinal centers are specialized microenvironments within the primary follicle.
They are composed of rapidly dividing B cells called centroblasts, which form the dark zone.
As centroblasts mature, they become non-dividing centrocytes, which form the light zone.
FDCs in the light zone present antigens to centrocytes.
TFH cells are present in the light zone and contribute to antigen-mediated selección of centrocytes.

Affinity Maturation

Somatic hypermutation introduces mutations in the BCR genes of centroblasts.
Centrocytes with BCRs that exhibit increased affinity for the antigen survive, while those with decreased affinity undergo apoptosis.
This process drives affinity maturation of the B-cell response.

Isotype Switching

TFH cells secrete cytokines that guide B-cell isotype switching.
IL-4 promotes switching to IgE.
IFN-γ promotes switching to IgG.
IL-5 promotes switching to IgA.
IL-10 and IL-21 promote both plasma cell and memory B cell differentiation.

Plasma Cell and Memory B Cell Differentiation

TFH cells contribute to the differentiation of activated B cells into either plasma cells or memory B cells.
IL-10 and IL-21 drive the differentiation process.

Ellen Vitetta

Ellen Vitetta is a prominent immunologist who made significant contributions to our understanding of B-cell biology.

B cell negative selection

B cells are selected against if they react to self‐antigen, removing any cells that react to self‐antigen.
Cells that react to self-antigen are retained in the bone marrow, which contrasts with T cells where cells are killed directly.

B cell positive selection

B cells are selected for if they can bind to antigen directly.
T cells are also positively selected, but this occurs based on their ability to recognize self molecules.
B cells go through negative selection before positive selection, whereas T cells go through positive selection before negative selection.
After positive selection, B cells that can bind to antigen are allowed to leave the bone marrow and circulate in the blood.

B cell receptor editing

If a B cell reacts to self-antigen, the B cell receptor can be edited to change its specificity.

B cell types

B2 cells are the most common type and they are active in the immune response.
B2 cells have a broad range of epitopes that they can recognize due to the rearrangement of their heavy and light chains during development.
B2 cells respond more quickly to repeated exposure to an antigen due to a process called affinity maturation.
Changes in immunoglobulin isotypes can happen due to a process called isotype switching.
B2 cells are responsible for the formation of memory B cells.

Phases of development

The first phase of B cell development is defined by the process of receptor editing and focuses on selection processes.
The process of receptor editing happens before positive selection.
The second phase of development happens in secondary lymphoid tissues.
The third phase of development happens in the periphery.

B cell maturation

Immature B cells express IgM and leave the bone marrow.
Mature B cells express both IgM and IgD.
B cells circulate in the blood and lymph.
They will re-enter secondary lymphoid tissues to initiate an immune response.

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Description

This quiz covers the mechanisms of B-cell activation, including the role of B-cell receptors and co-receptors in signaling. It also explores the importance of CD4+ T follicular helper cells in mediating an effective immune response. Test your knowledge on the interactions between B cells and T cells in the adaptive immune system.